| First Author | Perez-Shibayama C | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 11 | Pages | 5192-200 |
| PubMed ID | 24778443 | Mgi Jnum | J:337029 |
| Mgi Id | MGI:6858874 | Doi | 10.4049/jimmunol.1302526 |
| Citation | Perez-Shibayama C, et al. (2014) IFN-gamma-producing CD4+ T cells promote generation of protective germinal center-derived IgM+ B cell memory against Salmonella Typhi. J Immunol 192(11):5192-200 |
| abstractText | Abs play a significant role in protection against the intracellular bacterium Salmonella Typhi. In this article, we investigated how long-term protective IgM responses can be elicited by a S. Typhi outer-membrane protein C- and F-based subunit vaccine (porins). We found that repeated Ag exposure promoted a CD4(+) T cell-dependent germinal center reaction that generated mutated IgM-producing B cells and was accompanied by a strong expansion of IFN-gamma-secreting T follicular helper cells. Genetic ablation of individual cytokine receptors revealed that both IFN-gamma and IL-17 are required for optimal germinal center reactions and production of porin-specific memory IgM(+) B cells. However, more profound reduction of porin-specific IgM B cell responses in the absence of IFN-gammaR signaling indicated that this cytokine plays a dominant role. Importantly, mutated IgM mAbs against porins exhibited bactericidal capacity and efficiently augmented S. Typhi clearance. In conclusion, repeated vaccination with S. Typhi porins programs type I T follicular helper cell responses that contribute to the diversification of B cell memory and promote the generation of protective IgM Abs. |
